Outcome measures of disease severity are often designed for RCTs to meet the requirements from regulatory authorities. However, these measures are not always useful for so called Real World Evidence, for follow-up in clinical practice and treatment guidelines.
This challenge is illustrated in a new publication about the outcome measure PASI used to measure the severity of the skin disease psoriasis. Traditionally, the primary endpoint in psoriasis RCTs has been the number of patients achieving a 75 percent reduction in the PASI compared to baseline, i.e. PASI75. The second generation biologics make Complete Skin Clearance an achievable treatment goal for people with psoriasis and PASI90 is therefore suggested to be the new standard endpoint RCTs of biologics for psoriasis.
The objectives of this study were to analyse in a real‐world setting: Firstly, what factors are associated with higher levels of treatment response to biologics. Secondly, the Health‐Related Quality of Life gains associated with different response levels in clinical practice.
Biologically‐naïve patients with PASI, and Health Related Quality of Life outcomes (DLQI and EQ‐5D) before and after initiation to biologics during registration in the Swedish Register for systemic treatment of psoriasis, PsoReg, were included (n=515). Patient characteristics associated with higher treatment response were analysed by regression analyses. Improvements in absolute PASI, DLQI and EQ‐5D were analysed in different PASI percent response levels.
High PASI percentage response was associated with higher PASI before switch and lower BMI. Health related Quality of Life improved in all responder groups, but the magnitude of improvements differed. Patients achieving Complete Skin Clearance (PASI100) had lower absolute PASI before switch than patients with almost cleared skin (PASI90). Consequently, PASI 100 patients had lower improvements in absolute PASI and thus lower Health Related Quality of Life gains than PASI90 patients.
Patients in clinical practice lack the “baseline” PASI values used in RCTs as they may switch directly from one treatment to another or stay successfully treated for a longer time period. Since PASI percentage change was largely dependent on absolute PASI before switch to biologics, treatment goals based on a relative measure, such as PASI75 or PASI90, are not suitable in RWE. Absolute PASI values would be more useful for follow‐up in clinical practice and for treatment guidelines.
British Journal of Dermatology, 2020 Apr; 182(4): 965-973
First online: 20 July 2019